CDC-9 Inactivated Rotavirus Vaccine (IRV) Intramuscular (IM) Phase 1 Clinical Trial in Healthy Adults

Rotavirus remains an important cause of gastroenteritis and accounted for 19% of diarrhea-related deaths worldwide in 2019, the majority of which were in low and lower-middle income countries. Although live-attenuated vaccines for rotavirus are available for infants, the immunogenicity and vaccine effectiveness in low- and middle-income countries, where morbidity is highest, is suboptimal. Developing rotavirus vaccination strategies with improved immunogenicity could be advantageous in resource-limited settings. To improve the safety and efficacy of oral rotavirus vaccines, Centers for Disease Control and Prevention (CDC) scientists have developed a human rotavirus strain CDC-9 (G1P\[8\]\^9) that grows to high titer in Vero cells and shows structural stability during manufacturing process. The strain is a single gene natural reassortant with the VP3 gene derived naturally from a G2P\[4\] virus and the other 10 genes from a G1P\[8\] virus, the most common genotype throughout the world. Purified CDC-9 particles when inactivated by heat and administered intramuscularly, induced strong serum antibody response, and showed dose sparing effect in mice and rats. This inactivated rotavirus vaccine (IRV) also induced intestinal immunity in mice and prevented fecal shedding in gnotobiotic pigs against rotavirus. When given in combination with inactivated polio vaccine in mice it did not impair immune responses to either rotavirus or poliovirus serotypes 1, 2, and 3. Vaccination with IRV has shown to be safe and immunogenic in animal studies. A rotavirus vaccine with greater efficacy and stronger immunogenic response could further reduce infant mortality and morbidity, and a parenterally administered rotavirus vaccine could minimize interactions from co-administration with polio vaccination. Given the lower immunogenicity and vaccine efficacy of the oral rotavirus vaccines currently licensed by the US and in developing countries and approved for use by the World Health Organization (WHO), the IRV presents an opportunity to further prevent rotavirus-associated gastroenteritis in infants. This will be a Phase 1, randomized, observer blinded, dose escalating, placebo-controlled clinical trial in which healthy adults (18 - 45 years of age) will receive inactivated IRV or placebo administered through intramuscular injection to determine the safety, reactogenicity, and immunogenicity. Cohorts of 25 individuals (20 vaccine recipients and 5 placebo recipients) per dose level will receive three intramuscular injections four weeks apart. The two dose levels of vaccine to test will be 3.75 microgram (μg) or 7.5 μg. Subjects will receive a total of 3 IRV doses at Days 1, 29, and 57. Subjects will be monitored for approximately 6 months after the third-dose vaccination. They will be followed for solicited (local and systemic) adverse events (AEs) through 7 days after each dose of vaccine. Unsolicited AEs will be collected through Day 85. Immunogenicity labs will be obtained before each vaccine dose, 7 days after each vaccine dose, 28 days after each vaccine dose, 35 days after the first dose, and at the last study visit on Day 237 (durability of response). Serious Adverse Events (SAEs) will be followed from Vaccination on Day 1 through the last study visit on Day 237.